CAS OpenIR
Hepatitis B core VLP-based mis-disordered tau vaccine elicits strong immune response and alleviates cognitive deficits and neuropathology progression in Tau. P301S mouse model of Alzheimer's disease and frontotemporal dementia
Ji, M; Xie, XX; Liu, DQ; Yu, XL; Zhang, Y; Zhang, LX; Wang, SW; Huang, YR; Liu, RT; Ji, Mei; Xie, Xi-xiu; Liu, Dong-qun; Yu, Xiao-lin; Zhang, Yue; Zhang, Ling-xiao; Wang, Shao-wei; Huang, Ya-ru; Liu, Rui-tian
2018
Source PublicationALZHEIMERS RESEARCH & THERAPY
ISSN1758-9193
Volume10
Abstract

Background: Truncated mis-disordered tau protein plays an important role in the pathogenesis of Alzheimer's disease (AD) and frontotemporal dementia (FTD). Tau(294-305), an epitope in the truncated tau, is essential for pathological tau-tau interaction and aggregation. A tau(294-305)-targeted approach may have beneficial effects in the treatment of AD and FTD. Methods: In this study, we genetically fused tau(294-305) epitope to the hepatitis B virus core protein (HBc) major immunodominant region (MIR) (with the resultant protein termed T294-HBc), and we subcutaneously immunized a Tau.P301S transgenic mouse model of FTD and AD with T294-HBc four times. The levels and characteristics of antibodies induced by T294-HBc were determined by enzyme-linked immunosorbent assay. The effect of T294-HBc on the cognitive deficits of Tau. P301S mice was tested using the Morris water maze test, novel object recognition, and a Y-maze test. Western blot analysis and IHC were applied to measure the effect of T294-HBc on tau pathologies and neuroinflammation in the mouse brains. Results: The results showed that T294-HBc self-assembled into HBc chimeric virus-like particles (VLPs) with tau294-305 displayed on the surface and that it induced high antibody titers specifically against the mis-disordered truncated tau. Further investigation showed that these antibodies simultaneously bound to microtubule-binding regions 1-4 (MTBR1-4) [tau(263-274), tau(294-305,) tau(325-336,) tau(357-368) and tau(294-305)(P301S)]. Moreover, T294-HBc VLP vaccination significantly ameliorated memory and cognitive decline; reduced the levels of AT8-positive tau, truncated tau monomer, and oligomer; attenuated microgliosis and astrogliosis; and rescued synaptic deficits in Tau.P301S transgenic mice. Conclusions: T294-HBc VLP vaccine elicited strong immune response and alleviated cognitive deficits and neuropathology progression in Tau. P301S mice, indicating that the T294-HBc VLP vaccine has promising therapeutic potential for the treatment of AD and FTD.

KeywordAlzheimer's Disease Virus-like Particles Frontotemporal Dementia In-vivo Hepatitis b Core Protein Neurofibrillary Degeneration Truncated Tau Corticobasal Degeneration Neurofibrillary Tangles Structural Determinants Virus-like Particles (Vlps) Truncated Tau Vaccine Immunotherapy Protein Pathology Tauopathy
SubtypeArticle
DOI10.1186/s13195-018-0378-7
WOS IDWOS:000435568600001
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/26690
Collection中国科学院过程工程研究所
Recommended Citation
GB/T 7714
Ji, M,Xie, XX,Liu, DQ,et al. Hepatitis B core VLP-based mis-disordered tau vaccine elicits strong immune response and alleviates cognitive deficits and neuropathology progression in Tau. P301S mouse model of Alzheimer's disease and frontotemporal dementia[J]. ALZHEIMERS RESEARCH & THERAPY,2018,10.
APA Ji, M.,Xie, XX.,Liu, DQ.,Yu, XL.,Zhang, Y.,...&Liu, Rui-tian.(2018).Hepatitis B core VLP-based mis-disordered tau vaccine elicits strong immune response and alleviates cognitive deficits and neuropathology progression in Tau. P301S mouse model of Alzheimer's disease and frontotemporal dementia.ALZHEIMERS RESEARCH & THERAPY,10.
MLA Ji, M,et al."Hepatitis B core VLP-based mis-disordered tau vaccine elicits strong immune response and alleviates cognitive deficits and neuropathology progression in Tau. P301S mouse model of Alzheimer's disease and frontotemporal dementia".ALZHEIMERS RESEARCH & THERAPY 10(2018).
Files in This Item:
File Name/Size DocType Version Access License
Hepatitis B core VLP(3636KB)期刊论文出版稿限制开放CC BY-NC-SAApplication Full Text
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Ji, M]'s Articles
[Xie, XX]'s Articles
[Liu, DQ]'s Articles
Baidu academic
Similar articles in Baidu academic
[Ji, M]'s Articles
[Xie, XX]'s Articles
[Liu, DQ]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Ji, M]'s Articles
[Xie, XX]'s Articles
[Liu, DQ]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.